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bioRxiv · 10.1101/2023.07.11.548482

Blood pressure lowering enhances cerebrospinal fluid efflux primarily via the lymphatic vasculature

Jukkola, J.·Kaakinen, M.·Singh, A.·Moradi, S.·Ferdinando, H.·Myllyla, T.·Kiviniemi, V.·Eklund, L.
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Abstract

BackgroundInside the incompressible cranium, the volume of cerebrospinal fluid (CSF) is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering (BPL) on fluorescent CSF tracer absorption into the systemic blood circulation. MethodsBPL was performed by an i.v. administration of nitric oxide donor sodium nitroprusside (5 {micro}g kg-1 min-1) or the Ca2+-channel blocker nicardipine hydrochloride (0.5 {micro}g kg-1 min-1) for 10 and 15 to 40 mins, respectively. The effect of BPL on CSF clearance was investigated by measuring the efflux of fluorescent tracers (40 kDa FITC-dextran, 45 kDa Texas Red-conjugated ovalbumin) into blood and deep cervical lymph nodes. ResultsNicardipine and sodium nitroprusside reduced blood pressure by 32.0 {+/-} 19.6% and 22.0 {+/-} 2.5%, while temporarily elevating in intracranial pressure by 14.0 {+/-} 6.0% and 11.6 {+/-} 2.0%, respectively. BPL significantly increased tracer accumulation into deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by BPL into the systemic circulation was markedly reduced (-66.7%) by ligation of lymphatic vessels draining into deep cervical lymph nodes. ConclusionsThis is the first study showing that CSF clearance can be improved with acute hypotensive treatment and that the effect of the treatment is reduced by ligation of a lymphatic drainage pathway. Enhanced CSF clearance by BPL may have therapeutic potential in diseases with dysregulated CSF flow.

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Jukkola, J., Kaakinen, M., Singh, A., Moradi, S., Ferdinando, H., Myllyla, T., Kiviniemi, V., Eklund, L.. 2023-07-12. Blood pressure lowering enhances cerebrospinal fluid efflux primarily via the lymphatic vasculature. https://doi.org/10.1101/2023.07.11.548482

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